Commentary
Video
Safety Considerations for Newly Approved IPX203
The panelists discussed the safety profile of IPX203, considering challenges with transitioning, dosing strategies, and monitoring and adjusting patients’ individual dosage.
Earlier this month, the FDA approved Amneal Pharmaceuticals’ investigational agent IPX203, an oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules, as a treatment for patients with Parkinson disease (PD). Marketed as Crexont, the therapy is an oral formulation CD/LD which includes immediate-release granules as well as extended-release pellets. In its announcement, Amneal noted it expects the oral treatment to be available to patients in the United States in September 2024.
Amneal’s CD/LD ER capsule product was approved based on data from the phase 3 RISE-PD clinical trial (NCT0300788), a double-blind study published in JAMA Neurology in August 2023. In the study, those treated with IPX203 at least 3 times per day (n = 256) showed a statistically significant improvement of 0.53 hours (95% CI, 0.09-0.97; P = .02) in daily good ON time relative to those on IR CD/LD (n = 250), who were dosed 5 times per day.
Following the approval, NeurologyLive® assembled a panel of movement disorder experts to discuss the downstream impacts of IPX203 as a new treatment for patients with PD. The panelists include Robert Hauser, MD, a professor of neurology at the University of South Florida and director of the Parkinson’s Disease and Movement Disorder Center, and Hubert Fernandez, MD, a neurologist and director of the Center for Neurological Restoration at the Cleveland Clinic.
In this segment, Hauser and Fernandez covered the safety profile of IPX203, including some of the practical challenges of transitioning patients from immediate-release leveodopa. While the safety profile of IPX203 is similar to that of traditional levodopa, the duo stressed that clinicians must carefully manage the dosing transition to avoid under- or overdosing, ensuring optimal patient outcomes.
Transcript edited below for clarity.
Robert Hauser, MD: What about safety issues? Do you want to talk a little bit about transitioning over from IR to IPX203?
Hubert Fernandez, MD: The beauty of this product, the genius of it, is that it takes the best medication we have with all the known benefits and side effects. By the way, we've been using this drug for decades. So, from a safety standpoint, we don't expect anything different, which is pretty much what the RISE-PD safety and tolerability results show. But it re-engineers the best medication we have so that it's delivered in a more optimal manner, and its duration of effect is longer. So, I think you get the best of both worlds—you get the simplicity, the known entity of the good and the bad of levodopa, and it maximizes the benefits of it. So, yeah, it's no surprise that the medication's side effects would be very similar to those you would get from immediate-release levodopa.
I think the major or likely practical safety or tolerability risk for this medication comes when clinicians and patients start learning how to transition from their standard immediate-release levodopa to IPX203. The learning curve poses some risks. We could undershoot in the beginning, or we could overshoot, and clinicians and patients might think it’s not the best drug for them—not because of the drug itself, but because of the conversion process.
Robert Hauser, MD: Yeah, I think the conversion was designed to be relatively simple. If we look at both the label and what was done in the study, for most patients—including those on 500 milligrams of levodopa per day or more—you look at the most frequently given IR dose, the individual dose, and you multiply it by 2.8 and give it three times a day. But I think, on the safety issues, you have to know that’s a starting dose, and you have to see how the patient does.
Firstly, is the individual dose enough to get a good benefit? If not, if it’s too low, they may still have a fair amount of Parkinsonian signs—slowness, stiffness, tremor, etc.—and you may need to increase the dose. If they have too much dyskinesia, you may need to decrease the dose. And once you have that dialed in—individual doses and the response—you have to see, well, what’s the duration of benefit? They may still have wearing off between doses, and then you may need to give the doses more frequently. So, it’s very important to, once you initiate it, get feedback from the patient pretty quickly—generally within one to three days or so—and make adjustments. So, I think that’s the most important thing for clinicians to be aware of.
